Shape-specific nanostructured protein mimics from de novo designed chimeric peptides

Area of Science:

• Biomimetic Nanotechnology
• Supramolecular Chemistry
• Protein Engineering

Background:

• Natural proteins self-assemble into functional nanoscale architectures.
• Designing synthetic globular protein mimics is challenging due to control over building block interactions.
• Previous success focused on fibrous protein mimetics, leaving globular designs less developed.

Purpose of the Study:

• To develop a strategy for constructing shape-specific nanostructures resembling globular proteins.
• To investigate the self-assembly of chimeric peptides with defined folding motifs.
• To achieve precise control over the stoichiometry and geometric arrangement of synthetic building blocks.

Main Methods:

• Design and synthesis of chimeric peptides incorporating coiled coil dimer and collagen triple helix motifs.
• Induction of self-assembly under salt-free conditions.
• Characterization using small-angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations.

Main Results:

• Spontaneous self-assembly into monodisperse, trigonal bipyramidal-like nanoparticles.
• Precise control over the stoichiometry and relative arrangement of the two folding motifs.
• Coiled coil dimers formed the equatorial plane, while collagen triple helices occupied the axial positions.

Conclusions:

• Chimeric peptide design enables the creation of discrete, protein-like nanoparticles with controlled geometry.
• Molecular folding and geometric packing are critical for nanoparticle formation.
• This approach offers new pathways for engineering highly ordered, self-assembling protein mimics.